This invention relates to improved implant devices. More particularly, this invention relates to an improvement in infection-resistant drug delivery implants. A silicone fluid is utilized to form a uniform implant-adherent coating of an antimicrobial agent. The coatings applied in accordance with this invention are better retained on the implant surface during mechanized implant packaging operations and are effective to prevent infection which may otherwise result after implantation of the device.
The use of controlled-release implants for administering estradiol to ruminant animals has been described in U.S. Pat. No. 4,191,741. During implantation of such implants, conditions are typically unsanitary, causing infection which can result in loss of implants Use of an antibiotic or germicide layer or coating on the surface of the implant to reduce infections and to improve implant retention has been described in U.K. Pat. No.2 136 688 A. The antibiotic coating facilitates parenteral administration of the implants under non-sterile conditions; requirements for cleaning the implant needle, the site of implantation on the animal, and the implantation device are minimized or eliminated. Other infection-resistant implant materials have been described. See, e.g. U.S. Pat. No. 4,581,028 disclosing infection-resistant materials suitable for use as vascular grafts prostheses or other implanted devices.
It is known that antimicrobial agents can be layered or coated onto the surface of an implant to inhibit infection at the site of implantation. However, some difficulties have been encountered in implementing that technology. Surface-applied antimicrobial agents have been found to be easily dislocated from the surface of the implant by nominal mechanical manipulation of the implants, for example, during automated packaging operations. Loss of the antimicrobial coating dramatically reduces resistance to infection. Labor intensive recoating procedures and manual methods of packaging the antimicrobial coated implants have been employed to assure that implants have effective antimicrobial coatings at the time of administration. Even with added care during the implant manufacturing/packaging process, coating uniformity is difficult to control.
Greater efficiencies in the manufacturing and packaging of implants as well as greater infection resistance at the implantation site would be realized with greater uniformity and implant-adherence of coatings of antimicrobial agents for implants. There is a need in the art for an improved method of coating implants to produce more uniform and more durable antimicrobial coatings on the implant surface, which exhibit good stability during manufacture, handling, and storage, which allow immediate availability of the antimicrobial agents upon implantation and which do not interfere with the function of the implant.
In accordance with the present invention, a silicone fluid is employed to promote uniform adhesion of antimicrobial agents to the surface of an implant. The invention yields many advantages for the production and use of infection resistant implants. Greater efficiencies in implant manufacturing and processing operations are possible. The adherent antimicrobial coating does not easily shake off the implant surface, allowing the implants to be subjected to the more rigorous conditions of automated packaging operations. Redusting or recoating procedures are eliminated. Because the use of present invention results in a more consistent and higher level application of antimicrobial agent, less quality control/analytical time is required during manufacturing operations. Further advantages include improved appearance of the implants and coating consistency. Application of the coating of antimicrobial agent is not affected by normal variations in raw materials.
The present invention is based on the discovery that a silicone fluid can be applied to the exterior surface of an implant to improve the adherence of subsequently applied antimicrobial agents. The silicone fluid has a high affinity for the implant surface and spreads on the surface of the implant to form a thin film. The film serves as a matrix like carrier for subsequent applied antimicrobial agents, typically in a film-adherent powder or dust form. Antimicrobial agents contacting the silicone fluid layer are partially wetted by the fluid and retained on the surface of the implant.
In a preferred embodiment of the present invention an adherent antimicrobial coating is applied to an implant comprising an anabolic agent in a silicone polymer matrix adapted for sustained-release of the anabolic agent. The silicone fluid does not affect adversely either the safety or efficacy of the implant The rate of diffusion of the anabolic agent from the implant remains essentially unchanged after coating in accordance with this invention.
It is, therefore, an object of this invention to provide an implant having an improved antimicrobial coating.
A further object of this invention is to provide an improved adherent and more uniform antimicrobial coating for implanted devices.
Still a further object of this invention is to provide a process for the economical application of adherent coatings of antimicrobial agents on implant surfaces.